Visualizing thrombosis to improve thrombus resolution

Abstract

The severity, course, and outcomes of thrombosis are determined mainly by the size and location of the thrombus, but studying thrombus structure and composition has been an important but challenging task. The substantial progress in determination of thrombus morphology has become possible due to new intravital imaging methodologies in combination with mechanical thrombectomy, which allows extraction of a fresh thrombus from a patient followed by microscopy. Thrombi have been found to contain various structural forms of fibrin along with platelet aggregates, leukocytes, and red blood cells, many of which acquire a polyhedral shape (polyhedrocytes) as a result of intravital platelet‐driven contraction. The relative volume fractions of thrombus components and their structural forms vary substantially, depending on the clinical and pathogenic characteristics. This review summarizes recent research that describes quantitative and qualitative morphologic characteristics of arterial and venous thrombi that are relevant for the pathogenesis, prophylaxis, diagnosis, and treatment of thrombosis.

Understanding microvascular thrombosis in COVID-19 via massive single-cell imaging of circulating platelets

“…Our findings suggest that measuring the concentration and distribution of circulating platelet aggregates is a potentially effective approach to evaluating the potential risk of microthrombus formation. In fact, there are a number of postmortem examination reports showing that the primary cause of death in patients who died of COVID-19 pneumonia was respiratory failure due to diffuse alveolar damage with severe capillary congestion caused by microthrombi 10,16 . The strong correlation between the concentration of platelet aggregates and the oxygen administration severity and SpO2 levels (Figure 5a, Figure 6a, Figure 6b) strongly suggests our method's ability to detect precursors to widespread microthrombus formation.…”

“…Unfortunately, the underlying process of the incidence of COVID-19-associated microvascular thrombosis remains elusive. This is due to the lack of tools to statistically examine the detailed characteristics of platelet activity, or more specifically platelet aggregation (i.e., the initiation of thrombus formation) 15,16,17,18 in vivo. For example, optical microscopy 19 can directly probe platelet aggregation with high spatial resolution and has, in fact, visualized platelet hyperactivity in COVID-19 by identifying the presence of platelet aggregates (i.e., thrombus constituents) including macrothrombocytes 20 .…”

“…These results may suggest the presence of a non-negligible microvascular thrombotic risk that could not be detected by the D-dimer test. In other words, the D-dimer test mainly evaluates blood coagulation by measuring D-dimers that are produced either at the final stage of thrombus formation (i.e., cross-linking) or after thrombus degradation 32 and is known to be insensitive to microvascular thrombosis including TMA 35 , whereas our method characterizes the initiation of microthrombus formation and the degradation of microthrombi 15,16,17,18 . The latter method is, therefore, more sensitive with high resolution to platelet hyperactivity, which is a suggested mechanism of widespread microthrombus formation 2,41 .…”

Thrombolytic Enzymes of Microbial Origin: A Review

“…Dysregulation of the intrinsic balance between the coagulation cascade and the fibrin- and thrombolytic pathways can lead to severe outcomes such as myocardial infarction, stroke, and massive pulmonary embolism caused by fibrin accumulation in the blood vessel walls, resulting in the formation of hemostatic plug or a clot [ 1 ]. Currently, the tissue plasminogen activator (tPA) or plasminogen activator (PA) is an indispensable clinical tool in thrombolytic therapy [ 2 ].…”

Multimodality Characterization of the Clot in Acute Stroke

“…However, clots extracted from patients differ in size, heterogeneity, and compactness from the in vitro clots. Characterizing the clots extracted from patients with acute ischemic stroke can be important for understanding how the clot bio-physical properties relate to clinical imaging features, and how such features can be relevant for the diagnosis and treatment of AIS ( 29 ). Such understanding will render clinical imaging useful for instituting personalized treatment.…”